The immunopathogenesis of flea allergy dermatitis in dogs ...

[Pages:27]Veterinary Immunology and Immunopathology 99 (2004) 179?192

The immunopathogenesis of flea allergy dermatitis in dogs,

an experimental study

Melinda J. Wilkersona,*, Mary Bagladi-Swansonb, David W. Wheelerc, Kim Floyd-Hawkinsc, Carol Craiga, Kenneth W. Leed, Michael Drydena

aDepartment of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA bDepartment of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA cPfizer Animal Health, Veterinary Medicine R&D, 7000 Portage Road, MS 225-190-36, Kalamazoo, MI 49001, USA dHeska Corporation, 1613 Prospect Parkway, Fort Collins, CO 80525, USA

Received 7 October 2003; received in revised form 28 December 2003; accepted 9 February 2004

Abstract

In this study, we investigated the development of clinical disease and immune responses in the development of an experimental model of flea allergy dermatitis. Dogs were randomly divided into four treatment groups and were infested with fleas on two different feeding schedules (continuous and episodic). Group 1 consisted of four non-exposed dogs (negative controls) and Group 2 consisted of six dogs exposed to fleas continually. Groups 3 and 4 consisted of 14 dogs each that were exposed to fleas on an episodic schedule (two consecutive days every other week for 12 weeks). Group 4 also received intraperitoneal injections of a low dose of lectin (ricin) with immunomodulatory properties. The purpose of Group 4 was to investigate the effects of ricin on enhancing the development of clinical signs, flea antigen-specific IgE levels and altering the number of CD4? and CD8? T cell subsets in peripheral blood. Clinical signs developed in all flea exposed dogs, however, the dermatology lesion scores were less and shorter in duration for continuously exposed dogs compared to episodic exposed dogs, independent of ricin treatment. Lesion development was concentrated in the flea triangle and consisted principally of erythema, followed by alopecia, excoriation, papules, and crusts. CD4? and CD8? lymphocyte subsets or IgE levels were not altered by ricin treatment. Flea antigen-specific IgE values were highest in dogs exposed to fleas on a continuous basis compared to those episodically exposed. A greater percentage of clinical responder dogs with negative flea-specific IgE titers or negative intradermal test (IDT) were present in the episodic exposure groups than in the continuous exposure group. IgE titers corresponded slightly better with clinical responders than the IDT. The agreement between the IgE titers and IDT was good (weighted k ? 0:67). Histopathology of skin samples were consistent with a Type I hypersensitivity. In conclusion, we were able to develop a model of flea allergy dermatitis by experimentally exposing dogs to fleas on an episodic and continuous feeding schedule. In this study, continuously exposed dogs did not develop immunotolerance, and ricin did not enhance the development of FAD. # 2004 Elsevier B.V. All rights reserved.

Keywords: Flea allergic dermatitis; Flea allergen-specific IgE; Intradermal skin test; Lymphocyte subsets; Ricin

1. Introduction

* Corresponding author. Tel.: ?1-785-532-4818; fax: ?1-785-532-4072. E-mail address: wilkersn@vet.ksu.edu (M.J. Wilkerson).

Flea bite hypersensitivity, also called flea allergy dermatitis (FAD) is the most common skin allergy encountered in small animal veterinary medicine, the

0165-2427/$ ? see front matter # 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.vetimm.2004.02.006

180

M.J. Wilkerson et al. / Veterinary Immunology and Immunopathology 99 (2004) 179?192

immunopathogenesis of which has been little studied (Halliwell et al., 1987a; Halliwell and Schemmer, 1987b). Flea bite hypersensitivity manifests as pruritic dermatitis in animals that have become sensitized to antigenic material in flea saliva. Flea saliva contains a variety of histamine-like compounds, enzymes, polypeptides, and amino acids that span a wide range of sizes from 40 to 66 kDa (Halliwell et al., 1987a). They are also known to induce Type I, Type IV, and basophil hypersensitivity reactions. In general, most flea allergic dogs have immediate skin hypersensitivity (Gross and Halliwell, 1985). There are very few reports of experimentally induced models of flea allergic dermatitis in dogs (Gross and Halliwell, 1985; Halliwell, 1984a; Halliwell et al., 1987a; von Tscharner and Halliwell, 1990). In one study, five dogs were continuously exposed to fleas for 12 weeks and compared to two groups of five dogs exposed on an episodic basis. Dogs exposed on an episodic schedule developed positive intradermal tests and flea-specific IgE and IgG antibodies within 2?12 weeks, whereas the continuously exposed dogs developed allergic responses later and to a lesser degree (Halliwell, 1984a). Similar findings were noted in a later study in which groups of eight dogs intermittently exposed to fleas on a weekly schedule or three times weekly schedule developed positive skin tests within 3?8 weeks post-exposure, whereas continuously exposed dogs failed to develop positive skin tests. When the continuously exposed dogs were switched to an intermittent exposure at 24 weeks, they also developed skin test reactivity and antibody responses similar to the previous group of episodically exposed dogs (von Tscharner and Halliwell, 1990). In natural exposure settings, dogs that were continually exposed to high flea burdens or were completely flea na?ive had low IgE and IgG antibody levels and negative intradermal tests compared to flea-hypersensitive dogs (Halliwell and Longino, 1985; von Tscharner and Halliwell, 1990). These observations suggest that dogs exposed on a continuous basis may become partially or completely immunotolerant and that this immunotolerance may be broken when the dogs are switched to an intermittent exposure.

The objectives of this investigation were to develop an experimental model of FAD in the dog and to evaluate the differences in the development of clinical signs, immune responses and lesions in dogs exposed

to fleas on a continuous versus an episodic feeding schedule. In an attempt to create an immunotolerant group, six dogs were exposed to fleas on a continuous feeding schedule. To create the FAD model we exposed 28 dogs to fleas on an episodic basis. Nanogram amounts of a lectin immunomodulator, ricin were administered to half of the episodic exposed dogs with the intent of boosting flea-specific IgE production and enhancing the development of clinical signs associated with flea exposure. This strategy was based on previous studies that linked inhalation of castor bean dust by mill and dock workers with increased incidence of allergic disease (Thorpe et al., 1989), and that administration of ricin with an antigen induced enhanced production of IgE in animals that were inherently low IgE responders (similar to non-atopic dogs or people) (Diaz-Sanchez and Kemeny, 1991). Ricin has been shown to enhance IgE responses by preferentially inhibiting a population of regulatory CD8? T lymphocytes (Diaz-Sanchez et al., 1993) that tend to dampen IgE responses (Noble et al., 1993).

In this study, we used dermatological assessments, complete blood counts, CD4 and CD8 subset enumeration, flea antigen-specific IgE antibody responses, intradermal skin responses to flea antigens, and cytological and histological assessments of skin lesions to compare local and systemic responses to fleas in dogs exposed on continuous and episodic feeding schedules with or without concurrent ricin administration. We were able to identify differences in local and systemic responses among dogs developing FAD that were dependent on the feeding schedule, but independent of lectin exposure.

2. Materials and methods

2.1. Animals and housing

Female beagles were purchased from a Class A animal dealer and housed individually in cages or paired in runs. All dogs chosen for this study were greater than 1 year of age, because flea allergic dermatitis is rarely observed in dogs ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download